It is known that 5-aminolevulinic acid is useful for V B12 production, heme enzyme production, microbial culturing, porphyrin production and the like in the field of microbial fermentation, for infectious disease treatment (Non-patent Reference 1), sterilization, Haemophilus diagnosis, derivative materials, depilation, rheumatism therapy (Non-patent Reference 2), cancer therapy (Non-patent Reference 3), thrombus therapy (Non-patent Reference 4), diagnosis during cancer operation (Non-patent Reference 5), animal cell culture, UV cut, heme metabolism research, hair care, diagnosis of heavy metal toxication and porphyria, anemia prevention and the like in the field of animal therapy, and for agricultural chemicals and the like in the field of plants.
On the other hand, production method of 5-aminolevulinic acid is known only as its hydrochloride, and methods which use hippuric acid (Patent Reference 1), succinic acid monoester chloride (Patent Reference 2), furfurylamine (Patent Reference 3), hydroxymethylfufural (Patent Reference 4), oxovaleric acid methyl ester (Patent Reference 5) or succinic anhydride (Patent Reference 6) as the material have been reported.
However, since the 5-aminolevulinic acid hydrochloride contains hydrochloric acid, it is necessary to take into consideration corrosion of the apparatus and generation of a stimulation caused by the hydrogen chloride vaporized during the production process and compounding and dispersing process, so that it is preferable to take a countermeasure for preventing these.
Also, in the case of oral administration of 5-aminolevulinic acid hydrochloride or its application to the skin in human, a scorching stimulation is added to the tongue or skin. Accordingly, concern has been directed toward a 5-aminolevulinic acid salt having smaller stimulation than that of 5-aminolevulinic acid hydrochloride, as the 5-aminolevulinic acid to be used in the field of medicines.
In addition, since 5-aminolevulinic acid hydrochloride has a property to partially degrade at from 130 to 156° C. and completely degrade at 156° C., it has a problem of hardly able to withstand high temperature heat sterilization treatment.
A sterilization method by radiation exposure is known as a method for solving this problem (Patent Reference 7), but this method requires a radiation exposure apparatus.
Accordingly, in order to carry out sterilization by a general and convenient heat sterilization method, it is necessary to improve heat resistance of 5-aminolevulinic acid.
In addition, although 5-aminolevulinic acid hydrochloride is used in the field of plants (Patent Reference 8), when used by mixing with silver nitrate or the like bactericide component generally used for plants, precipitation of silver chloride is generated in some cases through the reaction of 5-aminolevulinic acid hydrochloride with silver nitrate, which requires great care from the operational point of view because of a possibility of disabling spraying of the agent due to clogging of the sprayer nozzle. Also, when an aqueous 5-aminolevulinic acid hydrochloride solution is directly applied to a fruit, coloring of the fruit sometimes becomes insufficient when chloride ion is present.
In addition, although an aqueous solution containing 5-aminolevulinic acid ion and nitrate ion has been suggested, 5-aminolevulinic acid nitrate has not been isolated yet (Non-patent Reference 6).
Patent Reference 1:JP-A-48-92328Patent Reference 2:JP-A-62-111954Patent Reference 3:JP-A-2-76841Patent Reference 4:JP-A-6-172281Patent Reference 5:JP-A-7-188133Patent Reference 6:JP-A-9-316041Patent Reference 7:JP-T-2001-514243Patent Reference 8:JP-A-4-338305Non-patent Reference 1:Peter W. et al., J. Am. Acad. Dermatol., 31, 678-680 (1994)Non-patent Reference 2:Kenneth T., U.S. Pat. No. 5,368,841 (1994)Non-patent Reference 3:Hillemanns P. et al., Int. J. Cancer, 85, 649-653 (2000)Non-patent Reference 4:Ichiro Yamada et al., Abstracts of Papers, The Japanese Orthopedic Association (1988)Non-patent Reference 5:Kamasaki N. et al., Journal of Japan Society for Laser Medicine, 22, 255-262 (2001)Non-patent Reference 6:Baxter C. S. et al., Toxicology And Applied Pharmacology, 47, 477-482 (1979)